1. Field of the Invention
The present invention relates to a transgenic rice for biosynthesizing resveratrol at high concentration, in which resveratrol synthase genes are expressibly inserted into the 12th chromosome of natural rice, and seed of rice produced therefrom. Further, the present invention relates to a health functional food composition, an animal feed composition, and a pharmaceutical composition for preventing and improving a metabolic disease, including seed of rice produced from resveratrol-enriched rice, in which resveratrol synthase genes are expressibly inserted into the 12th chromosome of natural rice.
2. Description of the Related Art
Recently in Korea, due to economical growth and a Westernized diet, an intake of fatty substances from foods has increased, and due to a lack of exercise, etc., metabolic diseases such as obesity, diabetes, hyperlipidemia, hypercholesterolemia, and arteriosclerosis have been increasing.
Obesity generally refers to a condition of excessively high body fat. It is regarded as obesity, when the ratio of body fat to the total weight is 25% or more for men and 30% or more for women. Obesity has been known as a direct or indirect cause of many lifestyle-related diseases such as diabetes, hypertension, hyperlipidemia, etc.
Diabetes is a type of a metabolic disease in which insulin secretion is deficient, dysfunctional, etc., (DeFronzo, 1988). It is characterized by hyperglycemia which relates to a high blood glucose level, and is a disorder causing various symptoms and signs due to hyperglycemia and glucose excretion in urine. Recently, due to an increase in obesity rates, especially in abdominal obesity, the incidence of diabetes has been exponentially increasing.
If such metabolic diseases are not properly treated, various abnormal symptoms are accompanied. Representatively, there are higher risks of renal disorders, neuropathies, strokes due to blood vessel disorders, kidney or heart diseases, diabetic foot ulcers, and cardiovascular diseases. These complications lower the quality of life, and ultimately shorten the lifetime of patients. Current methods of treating the metabolic disease include lifestyle modifications (a dietary therapy and an exercise therapy), a medicinal therapy, etc. However, it is difficult to strictly control or enforce a dietary therapy or an exercise therapy, and there are limitations in therapeutic effects. Therefore, the development of foods for treating a metabolic disease, etc., which may be easily applied in real life is greatly needed.
Meanwhile, resveratrol, a product of resveratrol synthase (RS) gene, is a product of phytoalexin which is one of defensive substances produced in response to environmental stress by external stimuli such as UV, pathogenic bacteria, wounds, etc., (Dercks and Creasy, 1989), and is biosynthesized by catalytic activity of resveratrol synthase (RS) using one molecule coumaroyl-CoA and three molecule malonyl-CoA (Rolfs and Kindl, 1984; Halton and Cornish, 1995).
Although resveratrol is found in more than about 72 types of plants such as grapes, mulberries, peanuts, lilies, etc., it is not biosynthesized at all in most major cereal crops such as rice, corns, wheat, etc., fruits, and vegetables (Aggarwal et al., 2004).
Further, besides the above-described effects of pharmacological actions, resveratrol is also known as a substance activating Sirt-1, a protein associated with life prolongation. Sirt-1 protein is one of proteins associated with life prolongation by prolonging life of cells, following activation by NAD+ in low-calorie conditions. According to Konrad et al. (2003), while Sirt-1 proteins are activated by NAD+ only when calories are limited, when resveratrol is added, Sirt-1 proteins are activated as in low-calorie conditions and increase the life span of yeasts by 70% on average when resveratrol is added in an experiment involving yeasts.
Resveratrol having such physiological activity is synthesized in more than 72 species of plants, and is always synthesized in woody plants such as pines, etc. However, in herb species, it is biosynthesized as a self-defensive substance in response to external stresses such as wounds by phytoalexin activity, damage by ozone, UV, pest infection, etc. Plants with the highest resveratrol biosynthesis are grapes and peanuts (Schroder et al., 1990).
Red wine contains resveratrol, and its consumption is negatively correlated with cardiovascular disease incidences. This is called the French Paradox (Wu et al., 2001) and led to worldwide attention on red wine.
Accordingly, in order to artificially increase the content of resveratrol, research has been conducted to inoculate grapes with strains during cropping, or to treat grapes and peanuts with ultrasonic cleaning or UV irradiation after harvest to increase the content of resveratrol.
Further, research has been conducted to develop crops for biosynthesizing resveratrol by introducing a resveratrol synthase gene isolated from grapes and peanuts via bioengineering methods. It has been reported that 182 μg/g of piceid (resveratrol glycoside) is produced in transformed kiwi plant leaves using a resveratrol synthase gene of grapes (Kobayashi et al., 2000), and 50 ng/g of resveratrol is produced in suspension culture cells of transformed tobacco using resveratrol synthase genes of peanuts (Hain et al., 1990).
P. Stark-Lorenzen et al. has reported that a transgenic rice is resistant to rice blast disease by introducing a stilbene (resveratrol) synthase gene originating from grapes into rice (Plant Cell Reports (1997) 16; 668-673).
Further, the present inventors have disclosed rice produced by introducing conventional resveratrol synthase genes of peanuts in rice (KR Patent Application Publication No. 10-2008-0012483). However, they merely confirmed that resveratrol was contained therein, and failed to provide any evidencing effects of improving metabolic diseases.
The present inventors developed transformed rice, which is a transgenic rice for biosynthesizing resveratrol, at high concentration by inserting resveratrol synthase genes of peanuts into the 12th chromosome of natural rice, and confirmed that there exist superior effects of improving a metabolic disease when resveratrol-enriched rice produced from the corresponding rice is ingested, compared to when the same amount of resveratrol is ingested, thereby completing the present invention.